TSLP is an immune cytokine that induces dendritic cell-mediated CD4+ T cell responses with a proallogenic phenotype. Dendritic cells activated by TSLP play crucial role in the induction and maintenance of allergic inflammatory Th2 by production of proallergenic cytokines, chemokines and costimulatory molecules that direct naïve T cells to become Th2 cells, producing IL-4, IL-5 and IL-13. Over-expression of TSLP in Atopic Dermatitis (AtD), Netherton Syndrome and asthma indicates a crucial role of this cytokine in the pathogenesis of these allergic inflammatory diseases. The use of TSLP antagonists for the treatment of allergic disease is under clinical investigation. The need exists for methods for monitoring the efficacy of treatment with TSLP antagonists. Such methods would preferably allow objective determination of a subject's disease state and/or response to treatment with a TSLP antagonist.
A “biomarker” is an objectively measured indicator that reflects the presence, progression, or successful treatment of a particular condition. Biomarkers have long been used in drug development, and the discovery and validation of new efficacy biomarkers is expected to improve the predictive disease models, reduce the time and cost associated with drug development, and increase the success rate of translating experimental drugs into clinical therapeutics. In addition, biomarkers are valuable in early detection of disease development, changes in disease status, and effectiveness of behavioral modifications and therapeutics in disease control.
The collection of proteins expressed during a disease (i.e., the disease proteome) is particularly useful for detection of disease, monitoring disease status, and evaluating effectiveness of therapeutics. Analysis of plasma for biomarkers is common due to the ease of accessibility, but biological fluids or tissues from the local site of pathology, known as “proximal fluids,” are often represent a more accurate state of the condition. Accordingly, there is a need for methods of monitoring the efficacy of treatment with a TSLP antagonist using a biomarker that is preferably detectable in proximal fluids.